Small interfering RNAs (siRNAs) and microRNAs (miRNAs) repress gene expression through nucleic acid base-pairing between the target mRNA and the small RNA guide bound to a member of the Argonaute family of proteins. The use of siRNAs and miRNAs to treat diseases and viral infections of non-hepatic origin requires designing siRNAs and miRNAs that effectively trigger gene silencing in vivo, resist nucleolytic degradation, and accumulate in the correct tissue and cell type. Presently, no current delivery strategy can effectively and selectively silence disease-causing or viral genes in some tissues but not others.
Accordingly, there is a need in the art for novel compositions for mediating gene silencing that can be administered systemically, but yet can act in a tissue specific manner.